8-68476982-C-G

Variant names:

• chr8-68476982-C-G
• rs1517114
• NM_052958.4:c.736+8162C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052958.4(C8orf34):​c.736+8162C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,898 control chromosomes in the GnomAD database, including 30,280 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30280 hom., cov: 32)
• Consequence: C8orf34 NM_052958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.947
• Publications: 17 publications found

Genes affected

C8orf34 (HGNC:30905): (chromosome 8 open reading frame 34) This gene encodes a protein that is related to the cyclic AMP dependent protein kinase regulators. Naturally occurring mutations in this gene are associated with an increased risk for severe toxicities, such as diarrhea and neutropenia, in patients undergoing chemotherapeutic treatment. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8orf34	NM_052958.4	c.736+8162C>G		intron_variant	Intron 4 of 13	ENST00000518698.6	NP_443190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8orf34	ENST00000518698.6	c.736+8162C>G		intron_variant	Intron 4 of 13	2	NM_052958.4	ENSP00000427820.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95257 AN: 151780 Hom.: 30265 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.633

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.627 AC: 95309 AN: 151898 Hom.: 30280 Cov.: 32 AF XY: 0.637 AC XY: 47298 AN XY: 74214

African (AFR) AF: 0.581 AC: 24052 AN: 41410

American (AMR) AF: 0.660 AC: 10094 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1824 AN: 3468

East Asian (EAS) AF: 0.885 AC: 4547 AN: 5140

South Asian (SAS) AF: 0.668 AC: 3213 AN: 4810

European-Finnish (FIN) AF: 0.712 AC: 7505 AN: 10538

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.617 AC: 41940 AN: 67934

Other (OTH) AF: 0.636 AC: 1344 AN: 2112

Alfa AF: 0.495 Hom.: 1397

Bravo AF: 0.619

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.44
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1517114; hg19: chr8-69389217;